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Anemia Ups and Downs: Agios Hit On One Drug, Touts Data For Another

Two days after news from one anemia drug program sent its stock down more than 20 percent, Agios Pharmaceuticals (NASDAQ: AGIO) is reporting promising data from a second anemia treatment.

In an interview, CEO David Schenkein downplayed the information, which emerged Thursday, that a healthy volunteer developed thrombocytopenia, or low platelets, after taking the experimental AG-519 for 14 days.

“This is a rare complication that occurs in many marketed drugs” like antibiotics, or blood pressure medications, Schenkein said. “We just happened to run into one case early in the drug’s development.”

Agios, of Cambridge, MA, has better news about a second anemia drug in development. At the European Hematology Association’s annual meeting in Copenhagen this weekend, the company is reporting that the drug, AG-348, led to “rapid and sustained” increases in oxygen-carrying hemoglobin in nine out of 18 patients with a genetic malfunction called pyruvate kinase deficiency.

This is an early look, however. Agios plans to accrue data from as many as 50 patients in the ongoing mid-stage trial and treat them all with either a low or high dose of AG-348 for six months. As of the March 27 cutoff date, 18 patients had been treated for at least three weeks, and of them, just three had taken the Agios drug for six months.

But Agios said that nine patients saw hemoglobin levels rise by at least 1.0 grams per deciliter of blood (g/dL), including two that were on AG-348 for six months. For those nine patients, the average rise was 3.4 g/dL and ranged from 2.3 g/dL to 4.9 g/dL.

People develop anemia for several reasons. Pyruvate kinase deficiency is rare, but it is potentially deadly, causing the body to improperly kill red blood cells.

The AG-348 data are the first to come from real patients, not just healthy volunteers.

Schenkein said the responses so far haven’t waned, and the drug has led to a “much higher increase” of hemoglobin than expected. But it’s too early to make definitive conclusions about the nine patients who haven’t responded. The median time to a hemoglobin boost of more than 1.0 g/dL so far has been 1.9 weeks on drug, but those responses occurred when patients were on AG-348 anywhere from 1.1 weeks to 9.1 weeks. “We’ll have to see if some of the ones who haven’t shown a response yet will [respond] with longer treatment,” he says.

Durably boosting hemoglobin in patients with severe cases of pyruvate kinase deficiency could help them avoid blood transfusions or complications like fatigue, jaundice, or a life-threatening accumulation of iron in their organs.

Pyruvate kinase turns sugar into energy in red blood cells. Without it, people can’t make enough healthy red blood cells, causing anemia. The anemia can be anywhere from mild to severe, but the only treatment options are supportive care, such as blood transfusions and iron chelation therapy to deal with the iron overload those transfusions can cause.

Patients may also need their spleens surgically removed, which can compromise the immune system’s ability to fight infections. There are no treatments approved specifically for pyruvate kinase deficiency, which affects less than 1 percent of the population, according to the National Organization for Rare Disorders.

Schenkein says Agios has seen enough to plan for a pivotal study, the last needed before potential regulatory approval.

Still, there are concerns. AG-348 binds not just to its target but also to a separate enzyme that impacts sex hormones. With today’s data, Agios reports an “upward trend” in testosterone in four male patients, and a “downward trend” in estradiol in five male patients. Considering AG-348 is a pill meant to be taken chronically for life, it’s important that those effects don’t lead to serious problems.

“It’s something to watch,” Schenkein says, though he adds that nothing of “clinical significance” has come from these trends as of yet.

Most side effects were considered mild. There was one case of osteoporosis in a patient that already had weak bones—commonly called osteopenia—at the start of the trial, according to Schenkein. No patients have dropped out of the study so far.

AG-348 is an important program for Agios, which wants to expand from its early work in cancer. Some of that work is co-owned by Celgene (NASDAQ: CELG), thanks to a wide-ranging alliance the companies first forged in Agios’s early days and then expanded last month.

Agios owns full rights to the drugs it’s developing for pyruvate kinase deficiency and other inborn errors of metabolism (IEM), inherited diseases that muck up the body’s ability to turn food into energy.

Today’s AG-348 data became more important after Agios reported Thursday that a single healthy volunteer in an early-stage study of AG-519 developed thrombocytopenia. Platelet levels returned to normal after the volunteer stopped treatment, suggesting AG-519 triggered the condition.

The disclosure spooked investors, who sent Agios’s shares down more than 20 percent in two days. Schenkein said, however, Agios believes the thrombocytopenia occurred because of an immune reaction, rather than the drug’s mechanism, and shouldn’t be a big concern going forward. The company’s plan is to move either AG-348 and AG-519 into late-stage testing. It’ll likely decide which of the two to advance later this year, Schenkein said.